A novel cannula design is proposed to provide distal perfusion during arterial cannulation. Arterial cannulation is common in several applications of extracorporeal blood processing, such as ArterioVenous Carbon Dioxide Removal (AVCO2R) treatment. AVCO2R is a respiratory treatment that uncouples oxygenation from CO2 removal by utilizing a low-resistance gas exchanger in a simple percutaneous arteriovenous shunt (i.e. pumpless) to achieve near-total extracorporeal removal of CO2 production. As in all extracorporeal applications that require arterial cannulation, complications such as infection and distal ischemia can occur. A unique distal perfusion cannula (DPC) is presented, where a 3-section balloon incorporated at the tip of the cannula acts as a vessel support, as well as a variable flow controller that ensures and regulates distal flow. This design approach allows for the cannula size to be maximized, which minimizes the resistance of the extracorporeal circuit, while ensuring safety for the patient. The DPC described here offers a simple, adjustable solution to femoral cannulation and will hold the key to the adoption and efficacy of AVCO2R, as well as other extracorporeal support therapies. In Phase I, computational techniques and in vitro experiments were used to design the distal perfusion cannula (DPC), and to fully characterize the prototypes. A functional, 3-section balloon prototype has been completed and verified of its ability to optimize both distal and cannula perfusion. The objective of Phase II is to construct a clinical quality DPC, and to verify that the cannula is successful in optimizing distal flow while minimizing complications on an in vivo animal model. At Phase II conclusion, manufacturability of the DPC will be defined, and the long-term functionality of the device will be determined. This grant will result in the development of a novel distal perfusion cannula (DPC) for use in arterial cannulation. The new DPC will optimize the performance of an extracorporeal circuit, while ensuring safety for the patient. [unreadable] [unreadable] [unreadable]